Anxiety is a psychiatric disorder that ranges in severity from very mild temporary disorders such as insomnia or stage fright to spontaneous panic attack with attending anticipation of doom or unreasonable terror. The benzodiazepine drugs are generally considered the drugs of choice for treatment of anxiety, although they are sometimes habituating and frequently cause ataxia and drowsiness. Buspirone is a new antianxiety drug which does not cause drowsiness, although it may cause headache or dizziness and sometimes nauses and diarrhea. Buspirone takes from one to two weeks to become effective, but it has advantages over the benzodiazepines in long term therapy by not causing functional impairment of the patient.
The ability of buspirone, a nonbenzodiazepine anxiolytic, to antagonize isolation-induced aggression in male mice at doses which do not produce debilitation [McMillen et al., Arch. Pharmacol. 335 454 (1987); McMillen et al., Drug Development Research 12 53 (1988)] is considered to be related to its recognition and action at the 5-HT.sub.1A receptor. The anxiolytic profile of additional nonbenzodiazepine compounds can be established by comparison of their activity profiles with that of buspirone in standard experimental test procedures.
N-(2-Methoxyphenyl)piperazine is a known compound. In the rat, it has been reported to be a metabolite of the antipsychotic agent millipertine [Caccia et al., Biochem. Pharmacol. 34 (3) 393 (1985)]. It has been shown to possess antihypertensive properties [Morphis et al., Proc. Soc. Exp. Biol. Med., 101 174 (1959)] and to block dopaminergic effects in the brain [Minard et al., J. Pharm. Pharmacol. 31 (2) 91 (1979)] and to block conditional avoidance responding (CAR) in the rat [Martin et al., Eur. J. Pharmacol. 156 223 (1988)], which is characteristic of antipsychotic agents.